Interstitial Lung Disease (ILD) is a general term that includes a variety of chronic lung disorders. When a person has ILD, the lung is affected in three ways. First, the lung tissue is damaged in some known or unknown way. Second, the walls of the air sacs in the lung become inflamed. Finally, scarring (or fibrosis) begins in the interstitium (or tissue between the air sacs), and the lung becomes stiff.
Breathlessness during exercise can be one of the first symptoms of these diseases. A dry cough also may be present. These are common symptoms that many people ignore. Someone with these symptoms may wait until they feel quite ill before going to the doctor. People with different types of ILD may have the same kind of symptoms but their symptoms may vary in severity. Their chest X-rays may look alike. Further testing is usually recommended to identify the specific type of ILD a person has. Some ILDs have known causes and some (idiopathic) have unknown causes.
ILD is named after the interstitium because this is the tissue affected by fibrosis (scarring). ILD is sometimes also known as “interstitial pulmonary fibrosis.” The terms interstitial lung disease, pulmonary fibrosis and interstitial pulmonary fibrosis are often used to describe the same condition and will be used interchangeably herein.
The course of these diseases is unpredictable. If they progress, the lung tissue thickens and becomes stiff. The work of breathing then becomes more difficult and demanding. Some of the diseases improve with medication if treated when inflammation occurs. Some people may need oxygen therapy as part of their treatment. The diseases may run a gradual course or a rapid course. People with ILD may notice variations in symptoms—from very mild to moderate to very severe. Their condition may remain the same for long periods of time or it may change quickly.
While the progress and symptoms of these diseases may vary from person to person, there is one common link between the many forms of ILD. They all begin with an inflammation. The inflammation may affect different parts of the lung, including the following: the walls of the bronchioles (bronchiolitis); the walls and air spaces of the alveoli (alveolitis); the small blood vessels (vasculitis).
Inflammation of these parts of the lung may heal or may lead to permanent scarring of the lung tissue. When scarring of the lung tissue takes place, the condition is called pulmonary fibrosis.
Fibrosis, or scarring of the lung tissue, results in permanent loss of that tissue's ability to transport oxygen. The level of disability that a person experiences depends on the amount of scarring of the tissue. This is because the air sacs, as well as the lung tissue between and surrounding the air sacs, and the lung capillaries, are destroyed by the formation of scar tissue.
Several causes of pulmonary fibrosis are known, including the following:
Infections: These include viral infections such as cytomegalovirus (a particular problem for people with compromised immune systems); bacterial infections, including pneumonia; fungal infections such as histoplasmosis; and parasitic infections.
Occupation and environmental factors: Long-term exposure to a number of toxins or pollutants can lead to serious lung damage. Workers who routinely inhale silica dust (silicosis), asbestos fibers (asbestosis) or hard metal dust are especially at risk of debilitating lung disease. So are people exposed to certain chemical fumes—sulfuric acid, for example—and ammonia or chlorine gases. But chronic exposure to a wide range of substances, many of them organic, also can damage your lungs. Among these are grain dust, sugar cane, and bird and animal droppings. Other substances, such as moldy hay, can be a problem when they cause a hypersensitivity reaction in the lungs (hypersensitivity pneumonitis). Even bacterial or fungal overgrowth in poorly maintained humidifiers and hot tubs can cause lung damage.
Radiation: A small percentage of people who receive radiation therapy for lung or breast cancer show signs of lung damage months (or sometimes years) after the initial treatment. The severity of the damage depends on how much of the lung is exposed to radiation, the total amount of radiation administered, whether chemotherapy also is used and the presence of underlying lung disease.
Drugs: Nearly 50 drugs can damage the interstitium of the lungs, especially chemotherapy drugs, medications used to treat heart arrhythmias and other cardiovascular problems, certain psychiatric medications, and some antibiotics.
Other medical conditions: ILD can occur with other disorders. Often, those conditions don't directly attack the lungs, but instead involve systemic processes that affect tissue throughout the body. Among these are connective tissue disorders and hematological diseases, including systemic lupus erythematosis, rheumatoid arthritis, dermatomyositis, polymyositis, Sjogren's syndrome and sarcoidosis.
Idiopathic pulmonary fibrosis: Although doctors can determine why some people develop ILD, in most cases the cause isn't known. Disorders without a known cause are considered a subset of ILD and are grouped together under the label idiopathic pulmonary fibrosis or idiopathic ILD. Although the idiopathic diseases have certain features in common, each also has unique characteristics.
Usual interstitial pneumonitis is the most prevalent of the idiopathic ILDs. Accounting for more than half of all cases, it's so common that the terms “usual interstitial pneumonitis” and “idiopathic pulmonary fibrosis” are often used interchangeably. Because usual interstitial pneumonitis develops in patches, some areas of the lungs are normal, others are inflamed and still others are marked by scar tissue. The disease affects twice as many men as women and usually develops between the ages of 40 and 70.
Although the names are nearly identical, pneumonitis is not the same as pneumonia. Pneumonitis is lung inflammation without infection, whereas pneumonia is lung inflammation that results from infection. In addition, pneumonia is generally limited to one or two areas of the lungs, but pneumonitis involves all five lobes—two in the left lung and three in the right.
Other, less common types of idiopathic pulmonary fibrosis include nonspecific interstitial pneumonitis, bronchiolitis obliterans with organizing pneumonia (BOOP), respiratory bronchiolitis-associated ILD, desquamative interstitial pneumonitis, lymphocytic interstitial pneumonitis, acute interstitial pneumonitis and bronchopulmonary dysplasia.
Shortness of breath is the main symptom of idiopathic pulmonary fibrosis. Since this is a symptom of many types of lung disease, making the correct diagnosis may be difficult. The shortness of breath may first appear during exercise. The condition then may progress to the point where any exertion is impossible.
Other symptoms may include a dry cough (without sputum). When the disease is severe and prolonged, heart failure with swelling of the legs may occur.
A very careful patient history is an important tool for diagnosis of idiopathic pulmonary fibrosis. The history will include environmental and occupational factors, hobbies, legal and illegal drug use, arthritis, and risk factors for diseases that affect the immune system. A physical examination, chest X-ray, pulmonary function tests, and blood tests are important.
Bronchioalveolar lavage (BAL), a test which permits removal and examination of cells from the lower respiratory tract, may be used to diagnose idiopathic pulmonary fibrosis. This test helps identify inflammation in lung tissue, and also helps exclude infections and malignancies (cancer) as a cause of a patient's symptoms. The test is done during bronchoscopy, a special examination of the lung.
A lung biopsy can also be performed, either during bronchoscopy or as a surgical procedure that removes a sample of lung tissue for your doctor to study. This procedure is usually required for diagnosis of idiopathic pulmonary fibrosis.
Other diagnostic tests for idiopathic pulmonary fibrosis include: blood tests, pulmonary function tests, chest x-ray and CT scan, to name a few.
There are several different treatment regimens for use in ILD and the related conditions, including the following:
Lung transplantation: This may be an option for younger people with severe forms of ILD who aren't likely to benefit from other treatment options. In order to be considered for a transplant, you must agree to quit smoking if you smoke, be healthy enough to undergo surgery and post-transplant treatments, be willing and able to follow the medical program outlined by the rehabilitation and transplant team, and have the patience and emotional strength and support to undergo the wait for a donor organ. The last is particularly important because donor organs are in short supply. In general, single-lung transplants are more successful in people with ILD than double-lung transplants are. And although many people who receive lung transplants enjoy a good quality of life, the survival rate is lower than it is for other types of transplants. Additionally, there is a quality of life issue with respect to the increased susceptibility to infection, high blood pressure, diabetes and cancer due to the life-long administration of the anti-rejection drugs.
Oxygen therapy: Although oxygen cannot stop lung damage, it can make breathing and exercise easier, prevent or lessen complications from low blood oxygen levels, and improve sleep and sense of well-being for afflicted patients. It can also reduce blood pressure on the right side of the heart. Children with ILD are especially likely to need oxygen therapy.
Cytotoxic drugs: Azathioprine, which is normally used to prevent organ rejection after a transplant, and the anti-cancer drug cyclophosphamide may be used to treat ILD by suppressing inflammation. The drugs are prescribed when corticosteroids fail to improve symptoms or, increasingly, as a first-line treatment in combination with corticosteroids. Cytotoxic drugs can cause severe side effects, including reduced production of red blood cells, skin cancer and lymphoma.
Antifibrotics: These drugs are used to help reduce the development of scar tissue. In clinical studies, these drugs have shown promise for slowing the progression of lung damage without suppressing the immune system, but real-world results have been disappointing.
Systemic corticosteroid drugs: Although systemic anti-inflammatory drugs, such as prednisone or methyl prednisolone, are the initial treatment of choice, they help only about one in five people with ILD. Those most likely to benefit have a non-idiopathic disorder and reversible changes in their lungs. Systemic corticosteroids seldom improve lung function in people with idiopathic pulmonary fibrosis. If benefits are shown, they are usually temporary in nature. In general, corticosteroid administration lasts for several months until symptoms improve, at which point the administration is tapered. Upon return of the symptoms, further steroid therapy or an immunosuppressive drug such as azathioprine may be recommended. Taken for long periods of time or in large doses, systemic corticosteroids can cause a number of side effects, including glaucoma, bone loss, high blood sugar levels leading to diabetes, poor wound healing and increased susceptibility to infection. Corticosteroids may be administered to treat the inflammation present in some people with IPF. The success of this treatment for many forms of pulmonary fibrosis is variable and is still being researched. Other drugs are occasionally added when it is clear that the corticosteroids are not effective in reversing the disease. Some doctors may use corticosteroids in combination with other drugs when the diagnosis is first established. Which drug treatment plan is effective and how long to use the drugs is the focus of current research.
Pulmonary complications after allogeneic hematopoietic cell transplantation (HCT) remain a major cause of morbidity and mortality. Among the estimated 50,000 to 60,000 hematopoietic cell transplantations performed each year (www.ibmtr.org), approximately 30% to 60% of the transplant recipients will experience a pulmonary complication (Cordonnier C et al., Cancer, 1986; 58:1047-1054; Jules-Elysee K et al., Am Rev Respir, Dis 1992; 146:485-491. A need exists in the field to develop a therapeutic alternative to combat the progression of ILD and the related conditions.